Department of Pediatrics and Amsterdam Lysosome Center 'Sphinx', Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Orphanet J Rare Dis. 2011 Aug 10;6:55. doi: 10.1186/1750-1172-6-55.
Mucopolysaccharidosis type I (MPS I) is a lysosomal storage disorder that results in the accumulation of glycosaminoglycans causing progressive multi-organ dysfunction. Its clinical spectrum is very broad and varies from the severe Hurler phenotype (MPS I-H) which is characterized by early and progressive central nervous system (CNS) involvement to the attenuated Scheie phenotype (MPS I-S) with no CNS involvement. Indication, optimal timing, safety and efficacy of the two available treatment options for MPS I, enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), are subject to continuing debate. A European consensus procedure was organized to reach consensus about the use of these two treatment strategies.
A panel of specialists, including 8 specialists for metabolic disorders and 7 bone marrow transplant physicians, all with acknowledged expertise in MPS I, participated in a modified Delphi process to develop consensus-based statements on MPS I treatment. Fifteen MPS I case histories were used to initiate the discussion and to anchor decisions around either treatment mode. Before and at the meeting all experts gave their opinion on the cases (YES/NO transplantation) and reasons for their decisions were collected. A set of draft statements on MPS I treatment options composed by a planning committee were discussed and revised during the meeting until full consensus.
Full consensus was reached on several important issues, including the following: 1) The preferred treatment for patients with MPS I-H diagnosed before age 2.5 yrs is HSCT; 2) In individual patients with an intermediate phenotype HSCT may be considered if there is a suitable donor. However, there are no data on efficacy of HSCT in patients with this phenotype; 3) All MPS I patients including those who have not been transplanted or whose graft has failed may benefit significantly from ERT; 4) ERT should be started at diagnosis and may be of value in patients awaiting HSCT.
This multidisciplinary consensus procedure yielded consensus on the main issues related to therapeutic choices and research for MPS I. This is an important step towards an international, collaborative approach, the only way to obtain useful evidence in rare diseases.
黏多糖贮积症 I 型（MPS I）是一种溶酶体贮积症，导致糖胺聚糖积累，导致进行性多器官功能障碍。其临床谱非常广泛，从严重的 Hurler 表型（MPS I-H），其特征为早期和进行性中枢神经系统（CNS）受累，到无 CNS 受累的衰减型 Scheie 表型（MPS I-S）不等。两种可用的 MPS I 治疗选择，酶替代疗法（ERT）和造血干细胞移植（HSCT）的适应证、最佳时机、安全性和疗效仍存在争议。为了就这两种治疗策略的使用达成共识，组织了一项欧洲共识程序。
一个专家组由 8 名代谢障碍专家和 7 名骨髓移植医生组成，他们都在 MPS I 方面具有公认的专业知识，参与了一项改良 Delphi 过程，以制定基于共识的 MPS I 治疗声明。使用 15 例 MPS I 病史来启动讨论，并围绕任何一种治疗模式做出决定。在会议之前和会议期间，所有专家都对病例（HSCT 是/否）发表了意见，并收集了他们决定的原因。由计划委员会编写的一套关于 MPS I 治疗选择的草案声明在会议期间进行了讨论和修订，直到达成完全共识。
在几个重要问题上达成了完全共识，包括以下内容：1）对于在 2.5 岁之前诊断出的 MPS I-H 患者，首选治疗方法是 HSCT；2）在具有中间表型的个体患者中，如果有合适的供体，则可以考虑 HSCT。然而，在这种表型的患者中，没有关于 HSCT 疗效的数据；3）所有 MPS I 患者，包括那些未接受移植或移植失败的患者，都可以从 ERT 中显著受益；4）ERT 应在诊断时开始，并可能对等待 HSCT 的患者有价值。
这项多学科共识程序就与治疗选择和 MPS I 研究相关的主要问题达成了共识。这是朝着国际合作方法迈出的重要一步，这是在罕见疾病中获得有用证据的唯一途径。
